The value of extended transurethral resection

BJUI BJU INTERNATIONAL

of bladder tumour (TURBT) in the treatment of
bladder cancer
Mario Richterstetter*, Bernd Wullich*, Kerstin Amann†, Lothar Haeberle‡,
Dirk Gerhard Engehausen*, Peter Juergen Goebell* and
Frens Steffen Krause*§
*Department of Urology, †Institute of Pathology, University Clinic, Erlangen, Germany, ‡Institute for Medical
Informatics, Biometry and Epidemiology, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany,
and §Department of Urology, General Hospital – AKh, Linz, Austria
Accepted for publication 9 November 2011

Study Type – Therapy (case series)
Level of Evidence 4
OBJECTIVE
• To analyse the impact of a standardised
extended transurethral resection of bladder
tumour (TURBT) protocol on the
determination of the residual tumour
status at initial TURBT session and
recurrence rate in the primary resection
area. Despite, the fact that there is a clear
consensus on the aims of TURBT, there is
little agreement on how to perform TURBT
to achieve that goal.
PATIENTS AND METHODS
• We retrospectively evaluated 221
consecutive patients, who underwent 305
TURBT sessions for bladder cancer,
including patients with recurrent tumours.
• All the TURBTs were extended by taking
additional deep and marginal specimens,
according to a standardised protocol.
• Clinical and histopathological data were
retrieved from the patients’ records.
What’s known on the subject? and What does the study add?
Transurethral resection of bladder tumour (TURBT) is the ‘gold standard’ in the
diagnosis and therapy of non-muscle-invasive bladder cancer. To improve the quality
of this technique an additional TUR (after 4–6 weeks) or a simultaneous photodynamic
diagnosis is often offered.
The present study shows different variables that influence, to a greater or lesser extent,
the accuracy of the TUR diagnosis and the success of the operation. This is very
important for the further management of bladder cancer, be it in tumour follow-up or
in preparation for more invasive therapies.
RESULTS CONCLUSIONS
• Across all tumour stages, residual • Extended TURBT provides detailed
tumour (pR1) was found in 38% of the information about the horizontal and
additionally taken specimens. vertical extent of the bladder tumour.
• There was a significant association of • The implementation of standardised
pR1 status with tumour stage, grade, and TURBT procedures, such as our protocol of
size. an extended TURBT, is greatly needed to
• Also in the group of non-muscle- improve local tumour control.
invading tumours, the rate of R1 resection • Whether a diagnostic re-TUR may be
was rather high at 22%. restricted to those cases with positive
• There was no association with focality margins or ground specimens remains to
and the training status of the surgeon. be studied.
• At follow-up, of all the patients with a
unifocal primary tumour there was KEYWORDS
recurrence in the same area as the primary
in 5.1%. TURBT, extended, residual tumour status,
recurrence rate

INTRODUCTION
The global age standardised incidence rate
of bladder cancer is 10.1 per 100 000 for
males and 2.5 per 100 000 for females [1].
In Europe, the highest incidence rate has
been reported in the Western and Southern
regions, followed by the Northern and
lowest in the Eastern European countries [2].
The global mortality rate among males is 4
per 100 000 vs 1.1 per 100 000 among
females [3]. At the time of diagnosis, ≈70%
of the patients harbour non-muscle-invasive
disease. Transurethral resection of bladder
tumour (TURBT) aims to treat and provide
an exact diagnosis (staging, grading, residual
tumour) for further therapeutic
management if necessary. Thus, the
technique of how to perform TURBT is
crucial in providing the pathologist with
informative samples for the evaluation of
the tumour’s extent. Unfortunately, until
now, there has been a lack of standards on
how to perform TURBT. The current

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RICHTERSTETTER ET AL.

guidelines of the European Association of FIG. 1. Model of the extended TURBT procedure,
TABLE 1 Histopathological report of all
Urology (2011) only address the indications including the collection of additional deep and
tumour-stages and their grading distribution
for when to perform simple vs fluorescence- margin specimens.
guided TURBT and diagnostic re-TUR, but do
N (%) G1, n G2, n G3, n
not give any details on the technical aspects Urothelium
pTa 145 (47.5) 86 48 11
of TURBT. Lamina propria
pT1 76 (24.9) 7 30 39
pT2 70 (23.0) 7 63 Muscle
In our department, a standardised extended Paravesical
pT3/4 8 (2.6) 1 7
TURBT protocol was developed in 2001, with fatty tissue
the objective of obtaining a higher certainty
in evaluating the extent of tumour
infiltration by taking additional specimens
from endoscopically ‘normal’-appearing TABLE 2 Distribution and localisation of the residual tumour correlated to the pT stage.
areas from the bottom and the margin of
the tumours. The aim of the present Positive Positive Bg, Positive Bm and Total, n (%)
retrospective study was to assess the Bm, n (%) n (%) or n/N Bg, n (%) or n/N or n/N
feasibility of our extended TURBT technique pTa 19 (13.1) 0 1 (0.7) 20 (13.8)
and to analyse its impact on the pT1 22 (28.9) 3 (4.0) 2 (2.6) 27 (35.5)
determination of clinically relevant pT2 14 (17.5) 18 (22.6) 25 (31.3) 57 (71.4)
parameters, e.g. residual tumour status (R) pT3/4 0 3/8 5/8 8/8
and recurrence rate in the primary resection
area.

PATIENTS AND METHODS
Between January 2003 and December 2004,
305 TURBT sessions (initial and re-TURBTs
due to tumour recurrence) from 221
consecutive patients were performed
in our department. The clinical and
histopathological data of the patients are
summarised in Tables 1 and 3 and the
evaluation was retrospective. A subgroup of
73 patients with an initial TURBT during the
above-mentioned interval and a tumour
recurrence during the follow-up period until
December 2008 were evaluated separately,
with a specific focus on the location of the
relapse in the bladder. All TURBTs were done
according to a standardised protocol (see
below). The mean (range) age at surgery was
68.2 (38–93) years. For this retrospective
analysis, we reviewed the medical records of
all patients, collecting clinical (age, sex,
tumour size and focality) as well as
histopathological data (stage, grade, R
status) and other variables such as surgeon’s
training status. All tumours were reviewed
according to the 2002 TNM classification [4].
An extended TURBT was performed, by four
experienced urologist and five junior
registrars under supervised conditions,
according to a standardised protocol (Fig. 1).
After completing the resection of the
tumour, additional specimens were taken
from the centre (bladder ground specimen
[Bg]) and from endoscopically ‘normal’-
appearing margin sites (bladder margin
specimen [Bm]) of the resection area.
Overall, three to four additional specimens
from the resection margin and one to four
deep specimens from the resection ground
were taken depending on the size of the
tumour. These specimens were sent to the
pathologist for separate evaluation of the
residual tumour status (pR0 vs pR1).
Data are shown as frequencies or
percentage. To examine the influence of the
various clinicopathological variables
(staging, grading, tumour size, focality) on
the residual tumour status, data were
compared using appropriate statistical tests.
The chi-squared test was used when all
expected frequencies were >5, the Fisher’s
exact test was used otherwise. The pR1
findings of an experienced urologist and a
junior registrar were compared with
McNemar’s test. All tests were two-sided.
Differences with a P ≤ 0.05 were considered
to be statistically significant after
Bonferroni-Holm multiple test correction to
address the multiple testing problem. All
statistical analyses were carried out using
the R system for statistical computing
(version 2.8.1; R Development CoreTeam,
Vienna, Austria, 2008).
RESULTS
The overall pR1 status with
histopathologically confirmed residual
tumour in the Bg and Bm specimens
accounted for 37.7% of all cases. In the
subgroup of the 227 non-muscle-invasive
tumours (pTa/T1/carcinoma in situ), the pR1
rate was 22.0%. In the pT2 and pT3/4
tumours the pR1 rate was 81.4% and
100.0%, respectively (P < 0.001, Fisher’s
exact test). Remarkably, the vast majority
(94%) of the pR1 findings were detected in
the Bm specimens. The distribution of
residual tumour across all cases is given in
Table 2. Considering tumour grade, G1
tumours had a pR1 status of 11.8%, G2
tumours of 28.9%, and G3 tumours of
64.2% (P < 0.001, chi-squared test).
For tumour size, three different groups were
defined: tumours of <3 cm (n = 190),
3–6 cm (n = 100), and >6 cm (n = 12). There
was a significant difference in the pR1
status between the three groups with
25.3%, 55.0%, and 10 of 12, respectively
(P < 0.001, Fisher’s exact test).
A pR1 status was found in 33.5% of the
TURBT specimens from resections of
unifocal tumours (n = 200), whereas
multifocal tumours (n = 105) had pR1
resections in 45.7%. Despite the obvious
difference, the P-value in the adjusted
analysis was P = 0.10 using the chi-squared
test, indicating only a minor effect on the
resection status in the multiple-tumour
setting.
There was no difference in the frequency
of pR1 findings irrespective of whether
the TURBT had been performed by an

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 VALUE OF EXTENDED TURBT FOR TREATING BLADDER CANCER
tumours depends on the completeness of
TABLE 3 Principal characteristics of 305
the performed TURBT. However, despite all
patients
surgical efforts aiming to achieve complete
tumour removal, the high recurrence rate
Characteristics Value
(35–70%) and thus the propensity of these
N (%):
lesions to eventually progress (10–50%)
Pathological staging:
represent the major obstacles of TURBT.
pTa 145 (47.5)
Besides tumour cell implantation and the
pT1 76 (24.9)
so-called ‘field effect’, insufficient resection
pT2 70 (22.9)
has also been discussed as a cause of
pT3/4 8 (2.6)
relapse particularly at the primary resection
pTis 6 (1.9)
site. Numerous trials investigating routine
Total 305
re-TURBT, as a diagnostic approach have
Grading:
reported detection rates of residual tumour
Grade 1 93 (31.1)
cells of 30–75% across all tumour stages
Grade 2 86 (28.7)
[6]. A long-term clinical study by Herr and
Grade 3 120 (40.1)
Donat [7] showed that the recurrence rate
Total 299
could be considerably reduced by an early
Tumour size:
re-TURBT. The authors concluded that early
Group A, <3 cm 190 (62.7)
re-TURBT might help to better evaluate the
Group B, 3–6 cm 100 (33.1)
putative risk of progression through better
Group C, >6 cm 12 (3.9)
staging.
Total 302
Focality:
Despite a clear consensus on the aims of
Unifocal 200 (65.6)
TURBT, most reports on the management of
Multifocal 105 (34.4) bladder cancer with TURBT, as part of the
Total 305 therapeutic approach, lack a description of a
Mean (range) age distribution, years: standardised method on how the procedure
All patients 86.2 (38–93) should be performed. In addition, with
Men 64.8 (38–86) the advent of newer techniques, e.g.
Women 70.2 (47–93) fluorescence-guided resection techniques
using photodynamic diagnosis (PDD), more
studies implementing standardisation of the
experienced urologist or by a junior registrar surgical method are warranted.
under supervised conditions (34.3% vs
41.2%; P = 0.28 chi-squared test). Among the attempts to better understand
the value of initial TURBT for the
Considering the value of extended TURBT on completeness of the resection are studies
local tumour control, we evaluated all investigating the amount of residual tumour
patients with a unifocal primary (n = 200) in specimens from early re-TURBTs. When
and their recurrent tumours (n = 28). The the initial resection was done because of
overall recurrence rate was 14.4%, with a non-muscle-invasive bladder cancer, the
recurrence in the same area as the primary percentage of pR1 in the re-TUR specimen
in 10 cases (5.1%) and 18 recurrent tumours varied between 15% and 45% for pTa
in other areas (9.2%). tumours and 33–58% for pT1 lesions [8–15].
These data indicate the need for an
improvement in the initial TURBT technique.
DISCUSSION In an attempt to compare different
techniques for the initial resection, Langbein
The aims of TURBT in bladder cancer are et al. [16] have shown that the pR1 status
two-fold. On the one hand, TURBT aims to after a routinely performed re-TUR was as
provide a potential cure of selected bladder high as 42% among all cases compared with
tumours. On the other hand, TURBT is 33% when an extended TURBT approach
important for accurate staging of ‘high-risk’ was applied.
tumours and particularly muscle-invasive
lesions, which require additional therapy To further improve initial TURBT, PDD was
including radical cystectomy or introduced and has been clinically approved
radiochemotherapy [5]. Successful surgical for >10 years. In a prospective, randomised
therapy of low-risk, non-muscle-invasive study, Filbeck et al. [17] showed a significant
© 2012 THE AUTHORS
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reduction in the tumour detection rate in
non-muscle-invasive tumours from 25.2%
to 4.2% in the re-TUR at 6 weeks after the
initial PDD-based TURBT. Similar findings
have been reported by other groups [18–20].
Despite the reduction of the R1 status with
the application of PDD, an effect on
progression or recurrence has not yet been
proven.
The present results clearly show that neither
pathological nor clinical parameters can
guarantee tumour-free resection by
conventional TURBT. Especially the rather
high pR1 rates of 16% in patients with pTa
tumours and of 38% in all patients with
non-muscle-invasive tumours including
carcinoma in situ necessitate an improved
TUR therapy also for these prognostically
favourable carcinomas. This could be
reached by TURBT using PDD, although in
cases with muscle-invasive lesions its effect
may be limited, as the fluorescence reaction
is solely restricted to the urothelium. Early
re-TUR or extended TURBT as performed in
the present study for the initial TURBT may
help to attain complete removal from the
deeper layers of the bladder wall. However,
the effect of extended TURBT in decreasing
the bladder tumour relapse rate remains to
be elucidated. The present observation of an
equilocal recurrence rate of 5% in unifocal
tumours, at least indicates an improved local
tumour control by our extended TURBT
approach.
Extended TURBT provides detailed
information about the horizontal and
vertical extent of the bladder tumour lesion.
The implementation of standardised TURBT
procedures, such as the present protocol of
an extended TURBT, is greatly needed to
improve local tumour control. Whether a
diagnostic re-TUR should be restricted to
those cases with positive Bms or Bgs
remains to be established.
CONFLICT OF INTEREST
None declared.
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Correspondence: Steffen Krause, Department
of Urology, Krankenhausstr. 9, General
Hospital – Akh, A-4020 Linz, Austria.
e-mail: steffen.krause@akh.linz.at
Abbreviations: TUR(B), transurethral
resection (of the bladder); Bg, bladder
ground specimen; Bm, bladder margin
specimen; PDD, photodynamic diagnosis;
EDITORIAL COMMENT
THE VALUE OF EXTENDED
TRANSURETHRAL RESECTION OF
BLADDER TUMOUR (TURBT) IN THE
TREATMENT OF BLADDER CANCER
Richterstetter et al. describe their experience
with an extended transurethral resection of
bladder tumour (TURBT) protocol and report
the presence of disease surrounding the
primary tumour at initial TURBT. There has
been little change over the past several
decades in the methods by which bladder
tumours are managed endoscopically. TURBT
has a dual role: to provide an exact
diagnosis for tumour type, grade and clinical
stage, as well as a therapeutic role if the
tumour has not invaded the muscularis
propria. It is therefore critical that on initial
TURBT, the tumour(s) are removed in their
entirety. Numerous studies have shown that
after initial TURBT, there is at least a
15–40% chance of finding residual tumour
on re-TUR surrounding the initial tumour
bed (paper references 7–14). This fraction is
even higher if there was no muscle present
in the initial specimen. This suggests that in
many cases the initial TURBT was
inadequate in removing the entire tumour.
This is the case when we do not resect what
appears to be ‘normal’ urothelium
surrounding the tumour.
The surgeons in this series took additional
specimens from the tumour base (‘bladder
ground specimen’) as well as from
endoscopically ‘normal’-appearing margin
sites, which were sent to pathology as
separate specimens. Although it is fairly
standard to send additional deep specimens
from the tumour base, resection of normal
urothelium surrounding the tumour on
initial TURBT is probably not routinely
performed except perhaps during a
re-TURBT. Interestingly, most (94%) of the
residual tumours were detected in the
margin specimens. The recurrence rate for
unifocal primary tumours (200 cases) was
14.4%, far lower than historical controls.
This concept is underscored in some recent
studies using fluorescent cystoscopy,
showing a significant increase in detection
of non-invasive bladder tumours by using
photodynamic diagnostic equipment [1,2].
Whether this increased detection rate is
clinically meaningful has yet to be proven
definitively.
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